Multiple sclerosis (MS) is a complex disease of the central nervous system (CNS), which is believed to be immune-mediated. While CD4(+) T cells have been the main suspects for years, there is ample evidence that other immune cells (including those of the innate immune system) play a contributing or regulating role in this disease. After a general introduction, this review focuses on different immune cell subsets implicated in MS pathogenesis and on current and future possibilities to target them for therapeutic use.